The overall goal of the research of the group is to provide a better understanding of the regulatory networks that control critical cellular responses to environmental stresses. We are currently investigating cell cycle checkpoint responses to cellular damage from various environmental stresses and how defects in these responses can contribute to cancer. Intricate regulatory networks control stress-induced cell cycle checkpoints and these networks respond in a damage- and cell type-specific manner. Group members are presently studying the critical molecular events that regulate cell cycle checkpoint signaling following exposures to ionizing radiation (IR), ultraviolet (UV) radiation, oxidative stress and other environmental stresses. In addition, we are investigating the cellular specificity of these processes in normal human cells (e.g. diploid fibroblasts, lymphoid cells, and normal breast and lung epithelial cells) and cells with genetic alterations in cancer susceptibility genes, such as the gene mutated in ataxia telangiectasia (ATM). Three independent isogenic lines of normal and ATM-deficient breast epithelial cells have been established through stable shRNA knock-down techniques in order to obtain populations of mammary epithelial cells that differ only in their levels of ATM. Studies of DNA damage signaling in these cells has provided novel mechanistic insight into the function of the ATM, the related ATR protein kinase and the DNA-dependent protein kinase (DNA-PK) in the G2 checkpoint response to ionizing radiation induced cellular damage.